Human endogenous retrovirus type E antigen CT-RCC-1 (CT-RCC-1)

CT-RCC-1 is a tumor-associated antigen specifically expressed in clear cell renal cell carcinoma (ccRCC). It is a 10-amino-acid peptide with the sequence ATFLGSLTWK, derived from the human endogenous retrovirus type E (HERV-E) located on chromosome 6q. The antigen was originally identified in a patient who experienced significant tumor regression following allogeneic hematopoietic stem cell transplantation, where donor-derived T cells were found to recognize the peptide in an HLA-A11-restricted manner. Expression of the CT-RCC-1 antigen is highly restricted to ccRCC tissues and is driven by the loss of the Von Hippel-Lindau (VHL) tumor suppressor, which leads to the activation of HIF-2α and subsequent transcription of the HERV-E locus. Because of its high tumor specificity and lack of expression in normal tissues, CT-RCC-1 is a promising target for precision immunotherapy. Current therapeutic development focuses on T-cell receptor (TCR) engineered T cells (TCR-T) designed to recognize the HLA-A11/CT-RCC-1 complex. Clinical trials, such as those conducted by the National Institutes of Health (NIH), are evaluating the safety and efficacy of these autologous TCR-T therapies in patients with metastatic kidney cancer who carry the HLA-A11 allele. The target represents a novel class of antigens derived from the 'dark matter' of the human genome, specifically activated endogenous retroviruses.

Other names

CT-RCC-1 antigenHERV-E-derived antigen CT-RCC-1CT-RCC-1 peptideATFLGSLTWK peptideHERV-E antigen

Adoptive T-cell therapy using T-cell receptor (TCR) engineered T cells that specifically recognize the CT-RCC-1 peptide presented by HLA-A11 molecules on the surface of tumor cells, leading to targeted cytotoxic killing of the cancer cells.